The technique of peritoneal dialysis (PD) as an end stage renal disease (ESRD) replacement therapy is becoming more accepted. Currently in the United States, approximately 8% of patients requiring renal replacement therapy choose this modality of treatment. High technical failure rates diminish PD utilization globally, but especially in the US, where bicarbonate-based PD solution is unavailable. There are many causes, including peritoneal barrier (Pbarrier) exposure to lactate, low dialysate pH, high glucose, advanced glycation end products (AGE), glucose-degradation products (GDP) generated from peritoneal dialysis fluid (PDF) heat sterilization, inflammatory foreign-body response to the catheter, uremia, and peritonitis. Uremia induces considerable structural Pbarrier pathology. Prior to initiating PD, impaired peritoneal structural integrity from uremia is associated with Pbarrier pathology. However, during PD, further compromise is driven by continued oxidant injury, inflammation, and a crescendo of chemokine, cytokine, and growth factor elaboration by resident Pbarrier cells and infiltrating mononuclear cells.
PD limitations involve failure of the peritoneal membrane as a dialyzer, and particularly, failure of the peritoneal membrane to ultrafilter fluid. This is measured and defined by the peritoneal equilibration test (PET), with patients who have high normal or high values indicating pathology. However, while the measurement of a high or high normal PET indicates membrane pathology, the measure is not linked to pathological processes per se, and is not observed early enough in the process so that changes in prescription or modality can be implemented early to redress injury and optimally benefit patients. More rarely, the peritoneum fails in a process called encapsulating peritoneal sclerosis (EPS). This tends to be associated usually, but not always, with prolonged use of the modality (e.g., with the incidence increasing substantially with >10 years of PD performance) and with prior episodes of peritonitis. Although both high PET and EPS involve peritoneal membrane failure, high PET status can often be overcome by prescription changes, or, at worst, modality discontinuation with transfer to hemodialysis or transplantation, but EPS is often fatal. The pathophysiological relationship between the two processes is also poorly defined, and validated biomarkers for the early identification of the presence of these syndromes are not available.
Failure of the PD membrane as a dialyzer is not a universal phenomenon even after many years of treatment, although injury to the peritoneum imposed by using it as a dialysis membrane may be common. The only difference between failure and injury appears to be the degree to which the injury imposed by the technique varies. In some, only histologic injury is apparent; in others, injury induces functional membrane failure. When functional membrane failure occurs differs among affected individuals, and the risk factors for its occurrence are incompletely understood. Apart from biologic variation in responses of individuals, two key factors appear to convey risk. One factor is the occurrence of peritonitis, and a second is exposure over long periods of time to high concentrations of glucose in the dialysate. Both of these risk features can be addressed, but especially the latter, which can be modified by a change in dialysate prescription. Thus, the earlier one can identify peritoneal injury, the earlier one can change prescriptions to minimize injury, take measures to prevent or treat peritoneal injury, or, in extreme cases, discontinue PD and switch to another ESRD renal replacement modality. Validated biomarkers for early peritoneal injury and for peritoneal injury progression are currently not available. While the PET defines injury to the peritoneal membrane that significantly interferes with peritoneal membrane function, it does not address the pathophysiology of membrane failure.
Periostin, a member of a novel vitamin K-dependent gamma-carboxylated protein family characterized by the presence of fasciclin domains, is induced in processes and pathologies including cardiac embryogenesis, osteogenesis, adult cardiac disease, metastatic disease, tumor suppression, and acute and chronic renal injury. Periostin was initially identified in osteoblasts and acts as an adhesion molecule during bone formation, supports osteoblastic cell line attachment, and is involved in cell survival, proliferation, migration, and differentiation.